Radiation Mitigation and Normal Tissue Stem Cells
Radiation Mitigation and Normal Tissue Stem Cells
批准号:
9123525
负责人:
Frank Pajonk
金额:
$44.64万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
AcuteAffectAgeBiological AssayBiological ModelsBrainCell CountCellsChronic DiseaseDNA RepairDataEventExposure toFibrosisFundingG-Protein-Coupled ReceptorsGoalsHematopoietic SystemHourHumanIn VitroInflammationIntestinesKnock-in MouseLeadLifeLungMediatingMedical centerMusNeuraxisNeuronsNormal tissue morphologyNotch Signaling PathwayOrganOrganoidsPharmaceutical PreparationsPlaguePopulationRadiationRadiation ToxicityResearchResearch Project GrantsSignal PathwaySignal TransductionSmall IntestinesStem cellsStructureSurvivorsTestingTissuesWorkbehavioral studybody systemcrypt cellimprovedin vivoin vivo Modelintestinal cryptirradiationmass casualtynerve stem cellnestin proteinneurogenesisnovelradiation effectradiation responsereceptor-mediated signalingreconstitutionself-renewalstem cell population
中文摘要
项目总结
这项研究项目的长期目标是确定正常组织干细胞通过哪些机制
最初幸存下来的辐射是在体内扩张,以保持组织的完整性。这项提案的目标是
目的是揭示含有磺酰基哌嗪活性基团的药物缓解作用的机制。我们
将调查在应用这些技术后正常组织干细胞库的重建情况
缓释剂对肠道和中枢神经系统(CNS)中的干细胞群体有直接影响,或
通过为干细胞扩增提供允许的微环境来进行调节。使用体外和体内模型
急性和晚期辐射损伤的系统,我们将调查这些药物对
干细胞的扩增和可塑性,并揭示导致辐射缓解的潜在信号事件。
具体地说,我们假设含有磺酰基哌嗪活性基团的辐射缓蚀剂
之前的资助期,直接或间接影响肠道和中枢神经系统的正常组织干细胞数量
通过G蛋白偶联受体介导的信号转导。细胞效应的系统研究
化合物#15在缓解ARS和DEARE并揭示潜在机制方面将为
发现和理解治疗急性辐射综合征(ARS)和延迟的新型双功能缓释剂
急性辐射暴露的影响(DEARE)。这将对该领域产生广泛影响,因为它将揭示
可用于减轻多器官辐射损伤的正常组织干细胞的常见靶点
系统同时运行。
英文摘要
PROJECT SUMMARY
The long-term goal of this research project is to identify mechanisms by which normal tissue stem cells that
initially survive exposure to radiation are expanded in vivo to maintain tissue integrity. The goal of this proposal
is to uncover the mechanism of mitigation observed with drugs containing sulfonylpiperazine active groups. We
will investigate whether the reconstitution of the normal tissue stem cell pool seen after application of these
mitigators is a direct effect on the stem cell populations in the gut and central nervous system (CNS), or
mediated by providing a microenvironment permissive for stem cell expansion. Using in vitro and in vivo model
systems for acute and late radiation damage we will investigate direct and indirect effects of these drugs on
stem cell expansion and plasticity and uncover the underlying signaling events that lead to radiation mitigation.
Specifically, we hypothesize that radiation mitigators with sulfonylpiperazine active groups, identified in the
previous funding period, affect normal tissue stem cell populations in the gut and CNS directly or indirectly
through G-protein-coupled receptor-mediated signaling. The systematic study of the cellular effects of
compound #15 in mitigating ARS and DEARE, and uncovering the underlying mechanisms will lay ground for
finding and understanding novel dual function mitigators for acute radiation syndrome (ARS) and delayed
effects of acute radiation exposure (DEARE). This will have a wide impact on the field, as it will uncover
common targets on normal tissue stem cells that can be used to mitigate radiation damage on multiple organ
systems simultaneously.
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专著(0)
科研奖励(0)
会议论文
Utilizing Radiation-Induced Multi-potency to Increase the Efficacy of Radiotherapy
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批准号:10705985
-
项目类别:
-
资助金额:$50.79万
-
财政年份:2023
-
负责人:Frank Pajonk
-
依托单位:
Use of CTEP portfolio compounds to counteract phenotype conversion in GBM
-
批准号:10598714
-
项目类别:
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资助金额:$5.42万
-
财政年份:2022
-
负责人:Frank Pajonk
-
依托单位:
Use of CTEP portfolio compounds to counteract phenotype conversion in GBM
-
批准号:10737830
-
项目类别:
-
资助金额:$10.55万
-
财政年份:2022
-
负责人:Frank Pajonk
-
依托单位:
Use of CTEP portfolio compounds to counteract phenotype conversion in GBM
-
批准号:10366706
-
项目类别:
-
资助金额:$46.27万
-
财政年份:2022
-
负责人:Frank Pajonk
-
依托单位:
Use of CTEP portfolio compounds to counteract phenotype conversion in GBM
-
批准号:10544037
-
项目类别:
-
资助金额:$45.34万
-
财政年份:2022
-
负责人:Frank Pajonk
-
依托单位:
Project 3: Inhibition of radiation-induced phenotype conversion in glioblastoma
-
批准号:10225552
-
项目类别:
-
资助金额:$34.58万
-
财政年份:2017
-
负责人:Frank Pajonk
-
依托单位:
Project 3: Inhibition of radiation-induced phenotype conversion in glioblastoma
-
批准号:9983049
-
项目类别:
-
资助金额:$35.34万
-
财政年份:2017
-
负责人:Frank Pajonk
-
依托单位:
Glioblastoma, Glioblastoma Stem Cells and Radiotherapy
-
批准号:9196164
-
项目类别:
-
资助金额:$37.08万
-
财政年份:2016
-
负责人:Frank Pajonk
-
依托单位:
Erythropoietin and Breast Cancer Stem Cells
-
批准号:9056545
-
项目类别:
-
资助金额:$31.96万
-
财政年份:2012
-
负责人:Frank Pajonk
-
依托单位:
Erythropoietin and Breast Cancer Stem Cells
-
批准号:8507626
-
项目类别:
-
资助金额:$30.04万
-
财政年份:2012
-
负责人:Frank Pajonk
-
依托单位:
Erythropoietin and Breast Cancer Stem Cells
-
批准号:8657917
-
项目类别:
-
资助金额:$31.0万
-
财政年份:2012
-
负责人:Frank Pajonk
-
依托单位:
The 26S Proteasome in Cancer Stem Cells
-
批准号:8112507
-
项目类别:
-
资助金额:$31.0万
-
财政年份:2009
-
负责人:Frank Pajonk
-
依托单位:
The 26S Proteasome in Cancer Stem Cells
-
批准号:8287645
-
项目类别:
-
资助金额:$31.0万
-
财政年份:2009
-
负责人:Frank Pajonk
-
依托单位:
The 26S Proteasome in Cancer Stem Cells
-
批准号:8515342
-
项目类别:
-
资助金额:$29.14万
-
财政年份:2009
-
负责人:Frank Pajonk
-
依托单位:
The 26S Proteasome in Cancer Stem Cells
-
批准号:7793232
-
项目类别:
-
资助金额:$31.96万
-
财政年份:2009
-
负责人:Frank Pajonk
-
依托单位:
Project 3: Inhibition of radiation-induced phenotype conversion in glioblastoma
-
批准号:9752977
-
项目类别:
-
资助金额:$34.58万
-
财政年份:--
-
负责人:Frank Pajonk
-
依托单位:
Radiation Mitigation and Normal Tissue Stem Cells
-
批准号:8941363
-
项目类别:
-
资助金额:$46.17万
-
财政年份:--
-
负责人:Frank Pajonk
-
依托单位:
海外基金